The results of the STAR*D trial prompted the next follow-on effectiveness trial study for the treatment of MDD, "Combining Medications to Enhance Depression Outcomes (CO-MED)." The CO-MED trial, supported by this contract modification, addresses the following specific questions regarding the use of combination medication therapy: 1) Do patients who receive combination medication therapy as initial treatment for the onset of a depressive episode recover (reach remission) faster than patients who receive the more traditional single medication therapy? 2) Are patients who receive treatment initially with combination medications more likely to reach remission? 3) Is the durability of remission (i.e., sustainable recovery) more likely in patients who receive combination rather than mono medication therapy? It is expected that the Contractor will implement and carry out all clinical trials with expert scientific leadership, careful guidance and attention to human subjects regulations and good clinical practice guidelines, and in a timely manner. Implementation will include but may not be limited to all of the following tasks: -- Obtain medication for the trial; -- Set up randomization procedures; -- Create and distribute assessment instruments and study management operations procedures; -- Establish study-wide communications, such as conference calls, investigator meetings, site coordinator meetings; -- Collect the assessment data; -- Transmit the assessment data to the data management center; -- Edit the data and establish a system of query resolution; -- Provide for the timely locking of the dataset so that statistical analyses may be conducted in a timely fashion; -- Prepare a public access database and appropriate documentation to meet standards and guidelines for data sharing; -- Write appropriate journal level scientific articles addressing the primary questions as well as secondary and other moderator and mediator questions as are appropriate. -- It is expected that the database will be made publicly available between one and two years after the database is locked.